It is well known that brain injury results in the development of neurologic deficits through two mechanisms. The first of these is known as primary mechanisms. These occur at the time of the injurious event and include mechanical processes such as laceration, tearing, stretching and compression of nerve fibres. Little can be done for this type of injury once it has occurred. The second mechanism is secondary injury, which includes biochemical and physiological processes, initiated by a primary injury but which manifest with time after the injury. It has been demonstrated that much of the morbidity after brain injury is associated with the development of this secondary injury. Given that the secondary injury develops from minutes to days after the primary event, there exists a window of opportunity to pharmacologically prevent this type of injury and significantly improve resultant outcome. However, the factors that make up secondary injury must first be identified and then “antifactors” developed to inhibit the injury process.
Our studies have concentrated on identifying secondary injury factors after brain injury and developing interventional therapies. One of the factors that we had previously identified1-4 as critical to determining outcome after injury was brain magnesium ion concentration. This ion is a regulatory factor in a number of biochemical and physiological processes that are activated after brain injury. Indeed, a decrease in the magnesium ion concentration was observed to exacerbate the injury process while an increase in the concentration of magnesium ion was noted to attenuate the injury process and result in an improved outcome5. The treatment of brain injury with magnesium has since been shown to be effective1,6-10 even when administered up to 24 hours after the primary event, and the success of the treatment in experimental animal studies has subsequently led to clinical trials in human brain injury.
Despite the attenuation of deficits after brain injury with magnesium administration, it was clear that there were still motor and cognitive deficits that persisted after the treatment. Our attention was particularly drawn to the fact that in younger animals, the accumulation of water in the brain (ie. cerebral oedema or brain swelling) was still present and that this may present a significant risk factor. Indeed, in a recent clinical study11, delayed brain swelling was responsible for 50% of all deaths recorded in young victims of brain injury.